79583-98-5

Usage

Uses

Used in Hydrogel Synthesis:
5-AZIDO-VALERIANIC ACID is used as a monomer in the synthesis of Chitosan-poly(ethylene glycol) hydrogels through azide-alkyne click chemistry. These hydrogels have potential applications in the biomedical field, such as drug delivery systems and tissue engineering scaffolds, due to their biocompatibility and tunable physical properties.
Used in Macrocycle Synthesis:
5-AZIDO-VALERIANIC ACID is used as a starting material for the synthesis of 5-iodo-1,2,3-triazole containing macrocycles. These macrocycles have potential applications in various fields, including supramolecular chemistry and the development of new pharmaceuticals, due to their unique structural properties and potential for molecular recognition.
Used in Drug Development:
In the pharmaceutical industry, 5-AZIDO-VALERIANIC ACID is used as a key intermediate in the synthesis of bivalent quinine dimers with an intervening triazole ring. These dimers are potential inhibitors of P-glycoprotein (P-gp) mediated cellular efflux, a mechanism that can lead to multidrug resistance in cancer cells. By inhibiting P-gp, these dimers may enhance the efficacy of chemotherapeutic drugs and help overcome drug resistance in cancer treatment.
Overall, 5-AZIDO-VALERIANIC ACID is a valuable chemical compound with diverse applications in the fields of hydrogel synthesis, macrocycle development, and drug design, particularly in the context of cancer treatment and overcoming multidrug resistance.

Upstream product

• 18622-31-6 cyclopentanone hydroperoxide 
• 14660-52-7 ethyl 5-bromovalerate 
• 14273-86-0 methyl 5-chloropentanoate 
• 591-80-0 pent-4-enoic acid 
• 2067-33-6 5-bromopentanoic acid 
• 79583-99-6 5-azidopentanoyl chloride 
• 21994-41-2 5-azidopentanenitrile 
• 5454-83-1 5-bromovaleric acid methyl ester 
• 862828-06-6 (4S)-3-[(2S)-5-bromo-2-methylpentanoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one 
• 127811-93-2 5-azidovaleric acid methyl ester 
• 89896-39-9 ethyl 5-azidovalerate 

Downstream Products

• 680-31-9 N,N,N,N,N,N-hexamethylphosphoric triamide 
• 1158174-59-4 C₁₁H₁₄N₄O₂ 
• 1314043-20-3 tert-butyl 2,2',2''-(10-(2-(4-((5-azidopentanamido)methyl)benzylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate 
• 1314043-22-5 2,2',2''-(10-(2-(4-((5-azidopentanamido)methyl)benzylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid 
• 1360130-72-8 5-azido-O-tritylpentahydroxamate 
• 1392285-43-6 C₄₉H₆₈N₁₀O₈ 
• 1392285-44-7 C₅₈H₇₇N₁₁O₉ 
• 1450755-79-9 C₃₄H₅₆N₆O₈S 
• 1450755-84-6 5-azido-N-(4-(dimethylamino)phenyl)pentanamide 
• 1409236-53-8 C₁₃H₂₁N₃O 

Relevant academic research and scientific papers

Conjugation of an oligonucleotide to Tat, a cell-penetrating peptide, via click chemistry

Uptake of diagnostic and therapeutic oligonucleotides that specifically target disease can be enhanced by attachment of a cell-penetrating peptide. Here, we describe the covalent attachment of an oligonucleotide to Tat, a biologically important cell-penetrating peptide, via click chemistry.

Linear-Dendritic Alternating Copolymers

Herein, the design, synthesis, and characterization of an unprecedented copolymer consisting of alternating linear and dendritic segments is described. First, a 4th-generation Hawker-type dendron with two azide groups was synthesized, followed by a step-growth azide-alkyne “click” reaction between the 4th-generation diazido dendron and poly(ethylene glycol) diacetylene to create the target polymers. Unequal reactivity of the functional groups was observed in the step-growth polymerization. The resulting copolymers, with alternating hydrophilic linear and hydrophobic dendritic segments, can spontaneously associate into a unique type of microphase-segregated nanorods in water.

Preliminary evaluation of 18F-labeled LLP2A-trifluoroborate conjugates as VLA-4 (α4β1 integrin) specific radiotracers for PET imaging of melanoma

Introduction: The transmembrane α4β1 integrin receptor, or very-late antigen 4 (VLA-4), is associated with tumor metastasis and angiogenesis, the development of chemotherapeutic drug resistance, and is overexpressed in multiple myelomas, osteosarcomas, lymphomas, leukemias, and melanomas. The peptidomimetic, LLP2A, is a high-affinity ligand with specificity for the extracellular portion of VLA-4 and several conjugates have been evaluated in vivo by NIR-fluorescence, 111In-SPECT and 68Ga- and 64Cu-PET imaging, but to date, not with 18F-PET. Methods: Using two highly stable organotrifluoroborate prosthetic groups: ammoniumdimethyl-trifluoroborate (AMBF3) and a new N-pyridinyl-para-trifluoroborate (N-Pyr-p-BF3), both capable of facile aqueous 18F-labeling by isotope exchange (IEX), we present the first PET imaging evaluations of two [18F]R-BF3 ?–PEG2-LLP2A tracers using VLA-4 overexpressing B16-F10 murine melanoma tumor mouse models. Results: Here, we demonstrate successful one-step 18F-labeling of both conjugates with wet NCA [18F]F? in radiochemical yields of up to 11.6% within 75 min at molar activities of 40–100 GBq/μmol. Average tumor uptake values based on ex vivo biodistribution values were 4.4%ID/g (11) and 2.8%ID/g (12) using 18F-labeled LLP2A-conjugates with the two prosthetic groups: N-Pyr-p-BF3 (5) and alkyl-N,N-dimethylammonio-BF3 (AMBF3) (7), respectively, and was found to be target-specific as evidenced by in vivo blocking controls. Dynamic PET scanning and biodistribution studies revealed slow clearance of the [18F]R-BF3 ?–PEG2-LLP2A tracers from the tumors, and also substantial uptake in the intestines, gall bladder, liver and bladder. Observed bone uptake was blockable, consistent with known VLA-4 expression in hematopoietic stem cells found in bone marrow. Conclusions: These studies show that these [18F]R-BF3 ?–PEG2-LLP2A conjugates (11 and 12) are promising VLA-4 targeting radiotracers, yet, further optimization will be required to reduce uptake in the gastro-intestinal tract.

Click chemistry to construct fluorescent oligonucleotides for DNA sequencing

"Click chemistry" 1,3-dipolar cycloaddition between alkynyl 6-carboxyfluorescein (FAM) and azido-labeled single-stranded (ss) DNA was carried out under aqueous conditions to produce FAM-labeled ssDNA in quantitative yield. The FAM-labeled ssDNA was succes

Hypervalent Iodine Based Reversible Covalent Bond in Rotaxane Synthesis

Reversible covalent bonds play a significant role in achieving the high-yielding synthesis of mechanically interlocked molecules. Still, only a handful of such bonds have been successfully employed in synthetic procedures. Herein, we introduce a novel app

Rapid formation of a supramolecular polypeptide-DNA Hydrogel for in situ three-dimensional multilayer bioprinting

A rapidly formed supramolecular polypeptide-DNA hydrogel was prepared and used for in situ multilayer three-dimensional bioprinting for the first time. By alternative deposition of two complementary bio-inks, designed structures can be printed. Based on their healing properties and high mechanical strengths, the printed structures are geometrically uniform without boundaries and can keep their shapes up to the millimeter scale without collapse. 3D cell printing was demonstrated to fabricate live-cell-containing structures with normal cellular functions. Together with the unique properties of biocompatibility, permeability, and biodegradability, the hydrogel becomes an ideal biomaterial for 3D bioprinting to produce designable 3D constructs for applications in tissue engineering.

Modulation of the Passive Permeability of Semipeptidic Macrocycles: N- And C-Methylations Fine-Tune Conformation and Properties

Incorporating small modifications to peptidic macrocycles can have a major influence on their properties. For instance, N-methylation has been shown to impact permeability. A better understanding of the relationship between permeability and structure is of key importance as peptidic drugs are often associated with unfavorable pharmacokinetic profiles. Starting from a semipeptidic macrocycle backbone composed of a tripeptide tethered head-to-tail with an alkyl linker, we investigated two small changes: peptide-to-peptoid substitution and various methyl placements on the nonpeptidic linker. Implementing these changes in parallel, we created a collection of 36 compounds. Their permeability was then assessed in parallel artificial membrane permeability assay (PAMPA) and Caco-2 assays. Our results show a systematic improvement in permeability associated with one peptoid position in the cycle, while the influence of methyl substitution varies on a case-by-case basis. Using a combination of molecular dynamics simulations and NMR measurements, we offer hypotheses to explain such behavior.

Design, synthesis and evaluation of novel ErbB/HDAC multitargeted inhibitors with selectivity in EGFRT790M mutant cell lines

Acquired resistance leads to the failure of EGFR TKIs in NSCLC treatment. A novel series of hydroxamic acid-containing 4-aminoquinazoline derivatives as irreversible ErbB/HDAC multitargeted inhibitors for NSCLC therapy had been designed and synthesized, which displayed weak anti-proliferative activity in several EGFR wild-type cancer cell lines (NCI–H838, SK-BR-3, A549, A431) yet retained moderate activity to EGFRT790M resistance mutation harboring NCI–H1975 cells. The mechanistic studies revealed that the representative compound 11e was able to inhibit the phosphorylation of EGFR, up-regulate hyperacetylation of histone H3 and even reduce the expression of EGFR and Akt in NCI–H1975 cells. In further assays, compound 11e also showed moderate anti-proliferative activity in other EGFRT790M harboring tumor cell lines (NCI–H820, Ba/F3_EGFR_Del19-T790M-C797S) and low toxicities in normal cell lines (HL-7702, FHC). This selectivity of designed multitargeted compounds could serve as a potential strategy to circumvent multiple mechanisms of acquired resistance to EGFR-targeted therapy without severe toxicities and side effects resulting from broad inhibition.

Discovery of triazolyl thalidomide derivatives as anti-fibrosis agents

Fibrosis with excessive accumulation of extracellular matrix (ECM) often causes progressive organ dysfunction and results in many inflammatory and metabolic diseases, including systemic sclerosis, pulmonary fibrosis, advanced liver disease and advanced kidney disease. The store-operated calcium entry (SOCE) pathway and the related signaling pathway were both found to be the important routes for fibrogenesis. Our aim in this study was to discover novel compounds to inhibit fibrogenesis. A number of triazolyl thalidomide derivatives were synthesized and evaluated for their anti-fibrosis activities. Compounds 7b-e, 8c-d, 10a-b and 10e inhibited intracellular Ca2+ activation and showed no cytotoxicity. Among them, 6-{4-[(3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl]-1H-1,2,3-triazol-1-yl}hexanoic acid (10e) with the most potent inhibitory effect was chosen for further examination. The results revealed that compound 10e, a SOCE inhibitor, reversed the migratory ability of TGF-β1-induced myofibroblasts, dedifferentiated myofibroblasts to fibroblasts due to cytoskeleton remodeling, and restrained myofibroblast activation by targeting Orai1 and TGF-β1/SMAD2/3 signaling pathways. The in silico study indicated that compound 10e, with the appropriate lipophilic carbon chain and carboxylic acid, showed a good drug-likeness model score. Conclusively, the SOCE inhibitor, compound 10e, is used as a promising lead compound for the development of a new treatment for fibrosis. This journal is

Chemical Targeting of Voltage Sensitive Dyes to Specific Cells and Molecules in the Brain

Voltage sensitive fluorescent dyes (VSDs) are important tools for probing signal transduction in neurons and other excitable cells. The impact of these highly lipophilic sensors has, however, been limited due to the lack of cell-specific targeting methods in brain tissue or living animals. We address this key challenge by introducing a nongenetic molecular platform for cell- and molecule-specific targeting of synthetic VSDs in the brain. We employ a dextran polymer particle to overcome the inherent lipophilicity of VSDs by dynamic encapsulation and high-affinity ligands to target the construct to specific neuronal cells utilizing only native components of the neurotransmission machinery at physiological expression levels. Dichloropane, a monoamine transporter ligand, enables targeting of dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential changes in a similar manner to the parent dyes, as shown by whole-cell patch recording. We demonstrate the feasibility of optical voltage recording with our probes in brain tissue with one-photon and two-photon fluorescence microscopy and define the signal limits of optical voltage imaging with synthetic sensors under a low photon budget determined by the native expression levels of the target proteins. This work demonstrates the feasibility of a chemical targeting approach and expands the possibilities of cell-specific imaging and pharmacology.